This application claims priority of Japanese Application No. 2000-094333 filed Mar. 30, 2000, the complete disclosure of which is hereby incorporated by reference.
This invention relates to an ion selective electrode employable for determining a concentration of a calcium ion and/or a hydrogen ion in an aqueous sample. In particular, the invention relates to an ion selective electrode for potentiometrically determining a concentration of a calcium ion and/or a hydrogen ion existing in body fluids such as blood and serum.
Various ions existing in body fluids, such as hydrogen ion, sodium ion, potassium ion, chloride ion, bromide ion, and iodide ion, can be quantitatively detected by means of an ion selective silver/silver halide electrode. Representative structure of the ion-selective electrode comprises, in order, an electro-insulating support, an electrode composite consisting essentially of a silver metal layer and a silver halide layer, an electrolyte layer, and an ion-selective membrane, the electrode composite being divided to give a pair of electrode units, and further comprising a reference liquid-receiving opening and a sample liquid-receiving opening each of which is provided on the ion-selective membrane of each electrode unit, and a bridge element having two terminals, one terminal being placed in the reference liquid-receiving opening and another terminal being placed in the sample liquid-receiving opening.
A composite ion selective electrode which comprises two or more ion selective electrode members in one structure is also known. The composite ion selective electrode is favorably employable for simultaneously determining concentrations of two or more different ions in a sample liquid.
Among the determination of concentration of various ions in a body fluid such as blood or serum, the determination of an ionic calcium is very important in the clinical test. The determination of an ionic calcium (i.e., calcium ion) in blood is necessary, for instance, when a patient is tested with respect to abnormal metabolism (for example, functional disorder of accessory thyroid or transfer of cancer to bone). Also important is the determination of concentration of hydrogen ion (in term of pH) in blood, because the pH value of the blood indicates an acid-base balance in the blood. Moreover, in most of the clinical tests, the ionic calcium concentration in blood is generally utilized after it is standardized in terms of a concentration value at pH 7.4. Therefore, it is of value that both of the calcium ion concentration and the hydrogen ion concentration are simultaneously determined in a simple procedure.
Since a clinical test device is frequently employed at home at the present time, it is advantageous that the ion selective electrode to be provided to the test device has a small size, as compared with the conventional ion selective electrode provided to the test device employed in hospitals or other medical treating facilities.
According to the study by the present inventors, most of the conventional ion selective electrodes, particularly, calcium ion selective electrodes and hydrogen ion selective electrodes give relatively poor analytical data. For instance, reproducibility of analytical data obtained in the use of different ion selective electrodes which have been produced using the same materials to give equivalent electrodes is not high. It is also noted that a response period for obtaining a constant analytical data is prolonged.
Accordingly, it is an object of the invention to provide a calcium ion selective electrode which shows good analytical reproducibility and which gives a constant analytical data within a short period of time after placing a sample liquid on the electrode.
Further, it is an object of the invention to provide a hydrogen ion selective electrode which shows good analytical reproducibility and which gives a constant analytical data within a short period of time after placing a sample liquid on the electrode.
Furthermore, it is an object of the invention to provide a composite ion selective electrode containing both of a calcium ion selective electrode and a hydrogen ion selective electrode, both of which show good analytical reproducibility and both of which give a constant analytical data within a short period of time after placing a sample liquid on the electrode. As a result of study of the present inventors, it has been discovered that the calcium ion selective electrode having a calcium ion selective membrane of a very small thickness gives good analytical results in the reproducibility of the analytical data and the response time. Further, it has been discovered the calcium ion selective membrane having a small thickness preferably contains calcium di[4-(1,1,3,3-tetramethylbutyl)phenyl] phosphate (t-HDOPP), particularly in combination with a vinyl acetate copolymer and dioctylphenyl phosphonate so as to obtain the analytical data of increased accuracy.
It is also discovered that the hydrogen ion selective electrode having a hydrogen ion selective membrane containing a combination of tri-n-dodecylamine and trisethylhexyl trimellitate (Tris EHT) gives analytical data with increased reproducibility. The hydrogen ion selective membrane preferably comprises a combination of tri-n-dodecylamine, trisethylhexyl trimellitate, potassium tetrakis(p-chlorophenyl borate), and a vinyl chloride-vinyl acetate copolymer, so as to increase analytical reproducibility.
Accordingly, the present invention resides in a composite ion selective electrode comprising
(1) a calcium ion selective electrode member and a hydrogen ion selective electrode member,
in which the calcium ion selective electrode member comprises an electro-insulating support, a pair of electrode units each of which comprises a silver layer and a silver halide layer, and which are electrically separated from each other, an electrolyte layer, and a calcium ion selective membrane, and
in which the hydrogen ion selective electrode member comprises an electro-insulating support, a pair of electrode units each of which comprises a silver layer and a silver halide layer, and which are electrically separated from each other, an electrolyte layer, and a hydrogen ion selective membrane;
(2) an electro-insulating member having two openings in which one opening is provided for introducing a sample liquid into the composite electrode and another opening is provided for introducing a reference liquid into the composite electrode;
(3) a pair of distributing members in which one member distributes the introduced sample liquid to the ion selective membrane of each ion selective electrode member at a site corresponding to one electrode unit and in which another member distributes the introduced reference liquid to the ion selective membrane of each ion selective electrode member at a site corresponding to another electrode unit; and
(4) a bridge member which is provided on the electro-insulating member to bridge the two openings of the electro-insulating member so as to electrically connect the introduced sample liquid and the introduced reference liquid;
which is characterized in that the calcium ion selective membrane has a thickness of 5 to 30 xcexcm, and the hydrogen ion selective membrane contains tri-n-dodecyl-amine and trisethylhexyl trimellitate.
The invention further resides in a calcium ion selective electrode comprising
(1) a calcium ion selective electrode member which comprises an electro-insulating support, a pair of electrode units each of which comprises a silver layer and a silver halide layer, and which are electrically separated from each other, an electrolyte layer, and a calcium ion selective membrane;
(2) an electro-insulating member having two openings which is provided on the calcium ion selective electrode member and in which one opening is provided for introducing a sample liquid into the composite electrode and another opening is provided for introducing a reference liquid into the composite electrode; and
(3) a bridge member which is provided on the electro-insulating member to bridge the two openings of the electro-insulating member so as to electrically connect the introduced sample liquid and the introduced reference liquid;
which is characterized in that the calcium ion selective membrane has a thickness of 5 to 30 xcexcm.
The invention furthermore resides in a hydrogen ion selective electrode comprising
(1) a hydrogen ion selective electrode member which comprises an electro-insulating support, a pair of electrode units each of which comprises a silver layer and a silver halide layer, and which are electrically separated from each other, an electrolyte layer, and a hydrogen ion selective membrane;
(2) an electro-insulating member having two openings which is provided on the hydrogen ion selective electrode member and in which one opening is provided for introducing a sample liquid into the composite electrode and another opening is provided for introducing a reference liquid into the composite electrode; and
(3) a bridge member which is provided on the electro-insulating member to bridge the two openings of the electro-insulating member so as to electrically connect the introduced sample liquid and the introduced reference liquid;
which is characterized in that the hydrogen ion selective membrane contains tri-n-dodecylamine and trisethylhexyl trimellitate.